Method of treating psoriasis with cycloheximide

ABSTRACT

Cycloheximide composition for use in treating psoriasis. Cycloheximide dispersed in a pharmaceutically acceptable topical carrier and topically applied to psoriasis affected area of skin.

United States Patent Montes 1 June 13, 1972 METHOD OF TREATING PSORIASIS[56] References Cited WITH CYCLOHEXIMIDE UNITED STATES PATENTS [72]Inventor: Leopoldo F. Montes, 4319 Kennesan 2,977,282 3/1961 Gray..424/268 Drive, Birmingham, Ala. 35213 3,014,840 12/1941 Vellaire....424/268 3,086,913 4/.1963 Hamilton ..424/268 [22] Filed: June 20,1969 Primary Examiner-Sam Rosen [21 1 Appl' 835330 Attorney-Jennings,Carter & Thompson 52 us. 01 ..424/268 [571 ABSTRACT [51] Int. Cl ..A6lk21/00, A6lk 27/00 Cycloheximide composition for use in treatingpsoriasis, [58] Field of Search ..424/268 Cycloheximide dispersed in apharmaceutically acceptable topical carrier and topically applied topsoriasis affected area of skin.

6 Claims, N0 Drawings METHOD OF TREATING PSORIASIS WITH CYCLOI-IEXIMIDEBACKGROUND OF INVENTION This invention relates to pharmaceuticalcompositions and the method of topically using the same for thetreatment of psoriasis and more particularly to the use of suchcompositions in which the primary active ingredient is cycloheximide.Cycloheximide (C H N is an antibiotic substance isolated from the beersof streptomycin producing strains of streptomyces griseus. It is veryactive against many yeasts and fungi but is tolerated in relatively highconcentrations by most bacteria. Heretofore, cycloheximide has not beenemployed for topical use and users have been warned that cycloheximideis a potent irritant and should be handled with caution to avoid contactwith unprotected skin. Such warnings usually include a statement thathands or other skin areas which have come into contact withcycloheximide should be immediately and thoroughly washed with soap andwater.

Although great advances have occurred in dermatologic therapy one majorskin disease, psoriasis, still lacks satisfactory treatment. The widelyused Goeckerman regimen (crude coal tar and ultraviolet lightirradiation) requires hospitalization, is not effective with everypatient and is not cosmetically acceptable. Another conventionaltreatment for psoriasis is steroids under occlusion. However, thistreatment is expensive and unpractical in generalized psoriasis and hasa significant incidence of after treatment relapses.

While some inhibitors of nucleic acid synthesis and protein synthesis(aminopterin, methotrexate) are useful in the systemic treatment ofpsoriasis, they have little or no effectiveness when topically applied.

SUMMARY OF INVENTION In accordance with my invention I form acomposition consisting of cycloheximide dispersed in a pharmaceuticallyacceptable topical carrier. The composition is topically applied to apsoriasis affected area of skin.

DETAILED DESCRIPTION OF INVENTION There are basic abnormalities inpsoriatic skin in that the epidermis in psoriatic lesions ischaracterized by an increase in the amounts of ribonucleic acid,desoxyribonucleic acid and protein, above the levels found in theepidermis of normal skin. Also, the epidermis in lesions of psoriasisshows pronounced hyperplasia, a large number of mitoses and a greatlyaccelerated turnover time of cell population.

I have found that cycloheximide exerts, with great intensity, a numberof biochemical effects which are opposite those increased in psoriasis.Cycloheximide inhibits synthesis of both protein and desoxyribonucleicacid. In some cells the inhibition of protein synthesis occurs byinhibition of the transfer of aminoacid from soluble ribonucleic acid tothe ribosomes and their subsequent polymerization into protein. Also,cycloheximide produces a blockage of mitosis at early prophase but notin late prophase or thereafter whereby cells in this stage continue theprocess of mitosis. Furthermore, the effects of cycloheximide arereversible which is a desirable property when treating a benigncondition.

In preparing my composition, the cycloheximide is the primary activeingredient and comprises from about 0.05 percent to 0.2 percent byweight of the composition. Preferably, the cycloheximide comprisesapproximately 0.1 percent by weight of the composition.

The following examples are illustrative of the method and products ofthe prevent invention, but are not to be construed as limiting.

EXAMPLE I 0.1 gram of cycloheximide is mixed with 100 grams of a vehiclein the form of a semisolid oil in water emulsion containing polyhydricalcohol esters, propylene glycol and liquid petrolatum. A suitable suchvehicle or base is sold under the trade name NEOBASE.

EXAMPLE 2 0.1 gram of cycloheximide is mixed with 100 grams of a vehiclecontaining 40 grams polyethylene glycol 4,000 and 60 grams polyethyleneglycol 400.

EXAMPLE 3 0.1 grams of cycloheximide is mixed with 100 grams of avehicle containing, by weight, 88.16 percent liquid petrolatum, 5.64percent polyethylene, 6 percent emulsifying agent, 0.1 percentantioxidant, and 0.1 percent preservative. A suitable such vehicle issold under the trade name PLASTIBASE l-IYDROPI-IILIC.

EXAMPLE 4 0.1 gram of cycloheximide is mixed with 100 grams of a vehiclein the form of a hydrophilic material containing high molecular hydroxylanimal fats. A suitable such vehicle is sold under the trade nameAQUAPHOR."

Preferably the vehicle is in the form of an ointment, paste or creamwhich does not spread easily beyond the limits of the the treated area.

The term topical as employed herein relates to the application of thecycloheximide, incorporated in a suitable base or vehicle, at the siteof the psoriasis affected area for exertion of local action.Accordingly, such topical compositions include those pharmaceuticalforms in which the cycloheximide is applied externally by direct contactwith the surface to be treated. By pharmaceutically acceptable carrieror base as used herein is meant the vehicle into which the cycloheximideis incorporated, the said vehicle comprising the variouspharmaceutically suitable additives for the purpose of facilitating theincorporation of the cycloheximide into the desired pharmaceutical form.

In testing my improved composition for treating psoriasis I first testedfor skin tolerance by applying my composition three times daily to theanterior aspect of the right forearm of six normal subjects, three beingmales and three being females. This testing period lasted for threeweeks during which time one subject developed mild erythema (redness) onthe 10th day which was temporary. The other subjects showed no reactionto the composition.

After the preliminary testing period, 10 patients, five males and fivefemales, with psoriasis were started on a treatment program wherein mycomposition set forth in Example I was applied two to three times perday. All subjects were private patients of the inventor. The results ofthis treatment are summarized in the following table:

SUMMARY OF DATA ON PATIENTS TREATED Patient Number Age Sex Duration ofTreatment Daily Applic.

14 days 14 days 21 days 28 days 21 days 14 days 21 days 19 days 35 days21 days Patient Number Area Treated Type of Degree of Lesion ImprovementPlaque Plaque Plaque Guttate Plaque Knee Elbow Knee Thigh Knee LllbwM 6Plaque Leg 50% 7 Plaque Elbow 25% 8 Guttate Knee 100% 9 Plaque Knee l 10Plaque Abdomen 75% from about 0.05 to 0.2 percent by weight of thecomposition.

2. The method of treating psoriasis affected area of skin as defined inclaim 1 in which the cycloheximide comprises approximately 0.1 percentby weight of the composition.

3. The method of treating psoriasis affected area of skin as defined inclaim 1 in which the carrier is a semisolid.

4. The method of treating psoriasis affected area of skin as defined inclaim 1 in which the carrier is a semisolid oil in water emulsioncontaining polyhydric alcohol esters, propylene glycol and liquidpetrolatum.

5. The method of treating psoriasis affected area of skin as defined inclaim 1 in which the carrier is polyethylene glycol.

6. The method of treating psoriasis affected area of skin as defined inclaim 1 in which the carrier comprises, by weight, approximately 88.16percent liquid petrolatum, 5.64 percent polyethylene, 6 percentemulsifying agent, 0.1 percent antioxidant and 0.1 preservative.

2. The method of treating psoriasis affected area of skin as defined inclaim 1 in which the cycloheximide comprises approximately 0.1 percentby weight of the composition.
 3. The method of treating psoriasisaffected area of skin as defined in claim 1 in which the carrier is asemisolid.
 4. The method of treating psoriasis affected area of skin asdefined in claim 1 in which the carrier is a semisolid oil in wateremulsion containing polyhydric alcohol esters, propylene glycol andliquid petrolatum.
 5. The method of treating psoriasis affected area ofskin as defined in claim 1 in which the carrier is polyethylene glycol.6. The method of treating psoriasis affected area of skin as defined inclaim 1 in which the carrier comprises, by weight, approximately 88.16percent liquid petrolatum, 5.64 percent polyethylene, 6 percentemulsifying agent, 0.1 percent antioxidant and 0.1 preservative.